WO2004035023A1 - Verwendung von formkörpern zur äusseren anwendung - Google Patents

Verwendung von formkörpern zur äusseren anwendung Download PDF

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Publication number
WO2004035023A1
WO2004035023A1 PCT/EP2003/010853 EP0310853W WO2004035023A1 WO 2004035023 A1 WO2004035023 A1 WO 2004035023A1 EP 0310853 W EP0310853 W EP 0310853W WO 2004035023 A1 WO2004035023 A1 WO 2004035023A1
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WO
WIPO (PCT)
Prior art keywords
shaped body
weight
solution
optionally
auxiliaries
Prior art date
Application number
PCT/EP2003/010853
Other languages
German (de)
English (en)
French (fr)
Other versions
WO2004035023A8 (de
Inventor
Stefan Frahling
Ralf Malessa
Original Assignee
Dr. Suwelack Skin & Health Care Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE2002148314 external-priority patent/DE10248314A1/de
Priority claimed from DE2003117982 external-priority patent/DE10317982A1/de
Application filed by Dr. Suwelack Skin & Health Care Ag filed Critical Dr. Suwelack Skin & Health Care Ag
Priority to US10/531,346 priority Critical patent/US9023333B2/en
Priority to EP03808702.9A priority patent/EP1551373B1/de
Priority to AU2003276011A priority patent/AU2003276011A1/en
Priority to ES03808702.9T priority patent/ES2529568T3/es
Priority to JP2005501273A priority patent/JP2006504799A/ja
Publication of WO2004035023A1 publication Critical patent/WO2004035023A1/de
Publication of WO2004035023A8 publication Critical patent/WO2004035023A8/de

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/733Alginic acid; Salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/04Antipruritics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/18Antioxidants, e.g. antiradicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00Anaesthetics
    • A61P23/02Local anaesthetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/04Alginic acid; Derivatives thereof

Definitions

  • the invention relates to the use of a shaped body containing at least one framework, with the exception of proteins, optionally one or more active substances and optionally one or more auxiliary substances for external use, a process for producing the shaped bodies mentioned and new shaped bodies.
  • the German patents DE 42 01 1 72, DE 42 01 1 73 and DE 42 01 1 79 describe pellets for pharmaceutical or cosmetic use which have scaffolders based on proteins.
  • the pellets are used in particular for the preparation of oral pharmaceutical formulations, the pellets are produced by dropping dispersions from the protein scaffolders and optionally cosmetic or pharmaceutical active ingredients into cryogenic inert liquids, preferably liquid nitrogen, and then separating the frozen pellets and freeze-drying.
  • cryogenic inert liquids preferably liquid nitrogen
  • the size of the pellets produced according to the aforementioned German patent specifications is specified in the general part of the descriptions with 0.2 to 1 2 mm, in the examples, however, the maximum size achieved is only 4 mm. This is an average size, i.e. the pellets are subject to more or less large size fluctuations,
  • molded articles of uniform shape and size are preferred, in particular for external cosmetic use.
  • the end user can easily use such molded articles handle, powder, or small pellets or irregularly shaped moldings are generally unsuitable for this purpose, efforts are being made to provide moldings of such a size that allow one dosage form to be used for each application, and also to convey larger moldings which, for example, have a colored design can become, even a stronger aesthetic impression,
  • Freeze-drying step includes, For example, EP-A-03521 90 discloses compositions consisting of solid and porous unit forms which comprise micro- or nanoparticles. These are produced, inter alia, by adding pastes to cavities in a mold and then performing a lyophilization The task of EP-A-03521 90 was oral Finding formulations with a taste mask that dissolve quickly in water. No topical application of the formulations is mentioned. Similarly, EP-A-0399902 discloses formulations produced by freeze-drying, which also serve to provide taste-masked, rapidly soluble pharmaceutical formulations. A-4758598 formulations produced by freeze-drying are known which are likewise used exclusively for oral use.
  • the object of the present invention was therefore to provide a new use of active substance-containing molded articles which have framework formers which are not based on proteins for external use.
  • the moldings should be relatively large, have sufficient cohesion, ie mechanical strength, be regularly shaped, easily dissolve when used on the skin and lead to a pleasant feeling for use.
  • shaped body in the sense of the invention is understood to mean a regularly shaped geometric body, for example, in particular spheres, cuboids, pyramids, stars but also shaped bodies which are modeled on natural shapes, such as, for example, those in the form of animals, such as sea animals, such as starfish, seafood, for example Mussels, etc. Plants and parts of plants, such as leaves, etc.
  • All of these molds are accessible by the process described below for producing the moldings used according to the invention.
  • a plurality of the moldings mentioned is also contained in a container. Mixtures of Acting moldings of different geometries.
  • the moldings can be packaged individually, but preferably in cosmetic use, in particular, a plurality of the moldings are present next to one another in contact in a container.
  • the volumes of the moldings used are not limited per se due to the method of their production.
  • the volumes are expediently at least about 0.1 cm 3 , preferably 0.3 cm 3 , more preferably at least about 0.5 cm 3 , even more preferably at least about 0.8 cm 3.
  • the volumes used are expediently up to about 6 cm 3 , preferably up to about 5 cm 3 , more preferably up to about 4 cm 3 , the size of the moldings is determined, among other things, by the location of the external use of the moldings, so use on larger areas of the body or on the hair ( e.g.
  • the diameter of a molding is expediently at least about 3 mm, preferably at least about 5 mm, more preferably at least some a 7 mm, more preferably at least about 8 mm to suitably about 60 mm, preferably about 50 mm, more preferably about 40 mm, even more preferably about 30 mm,
  • a particularly preferred shaped body has an essentially spherical geometry, the diameter of the sphere being between 3 and 30 mm, preferably between 5 and 20 mm, more preferably between 7 and 15 mm, even more preferably between 8 and 13 mm,
  • the molded body used according to the invention contains at least one scaffold, with the exception of proteins.
  • the scaffold is generally a so-called hydrocolloid, i.e. (Partly) water-soluble, natural or synthetic polymers that form gels or viscous solutions in aqueous systems.
  • the scaffolders are expediently selected from polysaccharides or synthetic polymers.
  • the scaffold former is preferably selected from the group of the polysaccharides.
  • Polysaccharides include, for example, homoglycans or heteroglycans, such as alginates, especially sodium alginate, carrageenan, pectins, tragacanth, guar gum, locust bean gum, agar agar, gum arabic, xanthan, natural and modified starches, dextrans, dextrin, maltodextrins, chitosan , Glucans such as ⁇ -1,3-glucan, ⁇ -1,4-glucan such as cellulose, mucopolysaccharides such as hyaluronic acid etc.
  • Synthetic polymers include for example: cellulose ethers, polyvinyl alcohol, polyvinyl pyrrolidone, synthetic cellulose derivatives such as methyl cellulose, carboxy cellulose, carboxymethyl cellulose .
  • Cellulose esters such as hydroxypropyl cellulose, polyacrylic acid, polymethacrylic acid, poly (methyl methacrylate) (PMMA), polymethacrylate (PMA), polyethylene glycols, etc. Mixtures of several framework formers can also be used. Alginates are particularly preferred according to the invention, and sodium alginate is particularly preferred.
  • Low-viscosity scaffolders in particular calcium-free sodium alginates, are preferred (sodium alginate with a calcium content ⁇ 3% by weight, more preferably ⁇ 2% by weight, even more preferably ⁇ 1.5% by weight), ie , such scaffolders, which preferably have a viscosity of less than 2000 mPas, more preferably less than 1000 mPas, most preferably less than 100 mPas (ie a solution of 1 g of the framework builder in 99 ml of distilled water (1% solution w / w ) at 20 ° C and a pH value of 6-8 has a viscosity of less than 2000 or 1,000 or 100 mPas).
  • low-viscosity scaffolders such as sodium alginate
  • the use of such low-viscosity scaffolders leads to easier solubility of the formulation or, when water is added, to a higher rate of disintegration or dissolution and thus to easier spreadability on the skin, in particular the use of low-viscosity types of alginate lead to a higher dissolution rate of the moldings used according to the invention
  • the polysaccharides preferably used according to the invention as scaffolders expediently have average molar masses of expediently from about 1 0 3 to about 1 0 8 , preferably about 1 0 4 to 1 0 7.
  • the scaffolders are compatible with the skin and preferably lead to formation when used on the skin of a film that has a protective function,
  • the shaped bodies used according to the invention optionally contain one or more active substances, preferably at least one active substance.
  • Active ingredients include, in particular, cosmetic or therapeutic or pharmaceutical active ingredients suitable for external use.
  • the shaped body used according to the invention preferably contains at least one cosmetic and / or pharmaceutical active ingredient.
  • the moldings used according to the invention are preferably Cosmetic or therapeutic agents, cosmetic molded articles or molded articles produced using cosmetic active substances within the meaning of the invention are essentially agents within the meaning of the Food and Consumer Goods Act (LMBG), ie substances or preparations made of substances that are intended to be used externally on humans be used for cleaning, care, or for influencing the appearance or body odor, or for imparting smell impressions, unless they are primarily intended to alleviate or eliminate diseases, conditions, physical damage or pathological complaints.
  • the cosmetic moldings used according to the invention are, for example, bath preparations, skin washing and cleaning agents, skin care products, in particular facial skin care products, eye cosmetics, lip care products, nail care products,
  • Foot care products in particular shampoos, hair conditioners, hair softeners etc., light stabilizers, skin tanning agents, depigmenting agents, deodorants, antihydrotics, hair removal agents, insect repellents, etc., or such agents in combination,
  • cosmetically optionally also, for example, dermatological, therapeutically active compounds include: antiacne agents, antimicrobial agents, antiperspirant agents, astringent agents, deodorant agents, depilatory agents, skin conditioning agents, skin-smoothing agents, agents for increasing skin hydration such as, for example, B, glycerol or urea, Sunscreens, keratolytics, free radical scavengers, antiseborrhoea, antidandruff agents, antiseptic agents, agents for treating the signs of aging and / or agents that modulate the differentiation and / or proliferation and / or pigmentation of the skin, vitamins such as vitamin C, agents with irritating side effects, such as alpha-hydroxy acids, beta-hydroxy acids, alpha-keto acids, beta-keto acids, retinoids (retinol, retinal, retinoic acid), anthralines (dioxyanthranol), anthranoids, Peroxides (especially benzoyl per
  • Enzyme inhibitors hydrating agents, skin soothing agents, detergents or foam-forming agents, and inorganic or synthetic matting fillers, abrasive agents.
  • Plant active substance extracts or extracts or individual substances obtained therefrom can also be mentioned.
  • the plant active ingredient extract is generally selected from the group consisting of solid plant extracts, liquid plant extracts, hydrophilic plant extracts, lipophilic plant extracts, individual plant constituents; as well as their mixtures, such as flavonoids and their aglyka rutin, quercetin,
  • Echinacea purpurea eg, alcoholic extracts, fresh plant sap, pressed sap
  • Eleutherococcus senticosus alkaloids
  • Rauwolfia e.g., Prajmalin
  • evergreen e.g. BNincamin
  • other phytopharmaceuticals Aloe, horse chestnut (e.g. aescin), garlic (e.g. garlic oil), pineapple (e.g. bromelaine), ginseng (e.g. ginsenoside), milk thistle fruits (e.g.
  • aqueous ethanol extract aqueous ethanol extract
  • phrosterols e.g. beta-sitosterol
  • wool flowers e.g. aqueous alcohol, extract
  • Drosera e.g., liqueur wine extract
  • sea buckthorn fruits e.g. juice obtained from them or sea buckthorn oil
  • marshmallow root primrose root extract
  • plantain eg pressed juice
  • nettle celandine, parsley
  • Plant extracts from ⁇ orolaena lobata Tagetes lucida, Teeoma siems, Momordica charantia, and aloe vera extracts
  • Preferred cosmetic active ingredients are natural and synthetic moisturizing factors such as, for example, glycerol, urea and ceramides, skin protection agents, skin whitening agents, vitamins, antioxidants, so-called antiaging agents, anti-irritants, sunscreen agents, etc.,
  • the therapeutically used shaped articles are those which contain at least one pharmaceutical or therapeutic, in particular also dermatological active ingredient and which are used in the sense of the Medicinal Products Act, among others These are intended to cure, alleviate or prevent illnesses, ailments, bodily harm or pathological ailments.
  • agents or active substances are intended for external use, which may be skin-active substances but also transdermal substances a: agent for the treatment of skin diseases, externally applicable analgesics, for example, dextropropoxyphene, pentazocin, pethidine, buprenorphine; Anti-inflammatory drugs / anti-inflammatory drugs (NSAIDs), for example, indomethacin, diclofenac, naproxen, ketoprofen, ibuprofen, flurbiprofen, salicylic acid and derivatives such as acetylsalicylic acid, oxicams; Steroid hormones, e.g. B. betamethasone, dexamethasone, methylprednisolone, ethinylestradiol, medroergotamine,
  • analgesics for example, dextropropoxyphene, pentazocin, pethidine, buprenorphine
  • Anti-inflammatory drugs / anti-inflammatory drugs for example, indom
  • dihydroergotoxine dihydroergotoxine
  • Gout agents e.g., benzbromarone, allopurinol
  • Dermatics externa including antibacterial agents, antifungals, antiviral agents, anti-inflammatory agents, antipruritic agents, anesthetic agents, e.g. benzocaine, corticoids, acne agents, anti-parasitic agents; topical hormones; Veins therapeutics; Immunosuppresives etc. all for external use.
  • Preferred therapeutic agents are analgesics, e.g. B.
  • Immunosuppressants hormones, agents for the treatment of skin diseases such as neurodermatitis, atopic dermatitis etc., and anti-herpes agents,
  • the frameworks in particular the polysaccharides, can also have certain therapeutic effects (for example, the preferred framework builder (sodium) alginate has a certain amount of antiviral activity), but they are not active ingredients in the sense of the invention.
  • the preferred framework builder (sodium) alginate has a certain amount of antiviral activity
  • auxiliaries include: surface-active agents in addition to the above-mentioned detersive surfactants, such as dispersants, emulsifiers, etc., fillers, pH adjusting agents, such as buffering agents, stabilizers, cosolvents, pharmaceutically and cosmetically customary or others Dyes and pigments, preservatives, plasticizers, lubricants or lubricants, etc. Squalane is a particularly preferred auxiliary.
  • the moldings according to the invention are used for external use in humans or animals.
  • the external application is such that the molded body according to the invention is moistened with water or an aqueous solution which contains one or more active substances and / or auxiliaries or is dissolved in water.
  • the molding can be completely dissolved to form a solution or disintegrate to form a gel. If the shaped body according to the invention is dissolved in a larger amount of water, it is generally a bathing application and this application is included in the external application according to the invention.
  • the present invention also relates to a Combination containing at least one of the moldings used according to the invention and at least one aqueous solution which contains one or more active substances and / or auxiliaries in an associated spatial arrangement (application package, set, kit-of-parts, etc.).
  • the active ingredient solution can be, for example, solutions of volatile active ingredients and / or auxiliaries that should not or cannot be introduced into the shaped body due to the manufacturing process by freeze-drying, such as certain proportions of essential oils, perfumes etc.
  • the amount and type of active ingredients and / or auxiliaries present additionally contain the shaped body used according to the invention preferably at least about 10% by weight of the framework, based on the total weight of the shaped body, preferably at least about 15, more preferably 30 more preferably at least about 50% by weight up to 100% by weight of the framework builder, in particular polysaccharides, such as sodium alginate,
  • the moldings generally also contain residues of water.
  • the water content can be up to 20% by weight.
  • the water content can change after the production of the shaped body by freeze-drying during storage, generally increasing.
  • the water content of the shaped body is preferred after production at about 2 to 15%, more preferably from 2 to 12% by weight, the moldings used according to the invention contain from 0 to 85% by weight, preferably from 0.000001% by weight to 50% by weight, % of one or more active substances, the proportions depend very strongly on whether the active substance is a cosmetic or therapeutic active substance, in particular the therapeutic active substances may be used in very small quantities,
  • the molded articles contain from 0 to 85% by weight of one or more auxiliary substances.
  • the molded articles can contain 0.1 to 70% by weight of the auxiliary substances, more preferably 5 to 60% by weight of auxiliary substances. Especially when used with an additional auxiliary substances.
  • Active ingredient solutions can also be used in molded articles which consist only of the hydrophilic scaffold and possibly additional auxiliaries,
  • a preferred auxiliary is squalane, which is a cosmetic oil.
  • the squalane surprisingly brings about an improved solubility of the shaped body, which facilitates external use on the skin. Squalane also has skin-care effects, although not an active ingredient in the sense of the invention.
  • the shaped body contains from about 10 to 60% by weight squalane (can be determined by extraction with diethyl ether using the Weibull Stoldt method in the official collection of ASU test methods according to ⁇ 35 LMBG)
  • the classification of the above-mentioned substances into the category of auxiliary substances in the context of the present invention does not exclude that these auxiliary substances can also have certain cosmetic and / or therapeutic effects.
  • a particularly preferred shaped body contains: at least 10% by weight of one or more Scaffolders, in particular polysaccharides, such as sodium alginate, in particular calcium-free sodium alginate, whose 1% by weight solution or suspension in water (1 g in 99 ml of water at 20 ° C., pH 6-8) preferably has a viscosity of less than 2000, preferably less than 1 000, particularly preferably less than 100 mPas, 0.000001% by weight up to 50% by weight of one or more active substances, 0.1 to 70% by weight% by weight of one or more auxiliary substances, such as in particular squalane, and up to 20% by weight, preferably up to 15% by weight, water, with the proviso that the shaped body has no proteins as scaffolders used
  • Shaped bodies such as that of the above-mentioned composition, containing at least one scaffolding agent, with the exception of proteins, optionally one or more active substances and optionally one or more auxiliary substances, for external use,
  • a volume of 0.1 cm 3 to 6 cm 3 preferably 0.8 cm 3 to 6 cm 3 , and a diameter (maximum distance between two points of the shaped body) of at least 6 mm,
  • the moldings used according to the invention are porous moldings with a homogeneous distribution of the ingredients (apart from any coatings which may be present),
  • the dissolution rate of the moldings used according to the invention is preferably less than 4 minutes, more preferably less than 1 minute (for moldings with a diameter of 9 mm is ⁇ 20 Seconds of complete hydration without a recognizable core),
  • the moldings used according to the invention can be obtained by a process which comprises the following steps: (a) preparing a solution or suspension which contains at least one biopolymer, possibly one or more physiologically active substances and possibly one or more auxiliary substances,
  • step (c) further steps can be carried out between these steps, in particular it is possible after step (c) to process the surface of the shaped bodies by mechanical processing or by spraying with e.g. Active ingredient solutions, dye solutions and / or the
  • the shaped body preferably does not have any
  • the procedure in the production is that an aqueous solution of the scaffolding agent is first prepared and then optionally one or more active ingredients or one or more auxiliary substances are added and mixed,
  • the solution or suspension it is necessary for the solution or suspension to have a certain concentration of the framework.
  • This concentration naturally depends on the type of used scaffolding agent, it is advantageously about at least 0.1% by weight, based on the total amount of the solution, preferably at least about 0.25% by weight up to about 20% by weight, preferably less than 15% by weight , more preferably less than 10% by weight (weight of the scaffold based on the total weight of the solution). Higher concentrations are not preferred, because then the viscosity of the solution becomes too high, which makes it difficult to process the solution.
  • the amount of the scaffolding agent contained in the solution or suspension has a decisive influence on the density (weight of the shaped body in relation to the volume of the geometric Shape of the shaped body) of the shaped body obtained, the density is in turn an important variable for the dissolution rate of the shaped body when moistened with water or an active ingredient and / or auxiliary substance solution, the higher the concentration of the scaffolding agent in the solution, the higher the density (the lower the degree of porosity) of the shaped body and vice versa.
  • the concentration of the framework in the solution or suspension prepared in step (a) is preferably selected from a range of about 0.25% by weight. -% to about 1 5% by weight, - Concentration of the preferably used scaffolding agent sodium alginate is preferably from 0.5 to 5% by weight, preferably 1 to 4% by weight.
  • the densities of the moldings used according to the invention are advantageously from about 0.01 g / cm 3 to 0.8 g / cm 3 , preferably from about 0.01 5 g / cm 3 to 0.5 g / cm 3 , preferably from about 0 .02 g / cm 3 up to 0.1 g / cm 3 , the term density, as used in the present case, denotes the weight of the shaped body in relation to the volume of the outer geometric shape of the shaped body. The weight of the individual shaped bodies depends, of course from his
  • the weight of the individual moldings is approximately 10 to 200 mg, preferably 20 to 100 mg.
  • balls with a diameter of 1 2 mm have a weight in the range from preferably 20 to 80 mg, more preferably 30 to 60 mg on, Corresponding preferred ranges are calculated for balls of different diameters,
  • the solution which is subjected to freeze-drying is preferably prepared in such a way that first a solution of the scaffolding agent is produced and then the active ingredients or auxiliaries which may be present are incorporated into the solution of the scaffolding agent. If oil-soluble active ingredients are used, these are preferably dissolved in oils which may be used as auxiliary substances (in particular squalane) and then added to the solution of the scaffolding agent.
  • This method of production has the advantage that stable solutions or suspensions are formed. No emulsifiers are required, and there is no phase separation of the solution or suspension during processing when oil-soluble or oily auxiliaries or active ingredients are used.
  • the solution prepared in this way is then poured into a mold which has the cavities of the desired geometric shapes corresponding to the moldings, the mold preferably consists of rubber, silicone rubber, vulcanized rubber (rubber) etc., preferred are rubber molds, the molding materials can optionally coated.
  • the cavities of the shaped bodies into which the solution is poured generally have the shape of the desired shaped body.
  • the volume of the cavity essentially corresponds to the volume of the moldings obtained later, since the volume of the solutions or suspensions filled into the cavities increases during freezing (difference in density between water and ice), the cavities are generally not completely filled, Completely symmetrical moldings are obtained in this way.
  • cryogenic solutions such as in liquid nitrogen
  • Such irregularly shaped moldings are just in the area the cosmetic end products are not desired.
  • these molded articles produced by the dropping process require mechanical finishing, which is not necessary according to the process as used according to the invention.
  • the solution or suspension is frozen.
  • the cooling or freezing of the solution itself can be carried out in any manner.
  • the cooling in the method used according to the invention is preferably carried out by blowing with cold air. Further methods include, for example, immersing the molds in liquid gases, such as, for example, immersing them in liquid nitrogen ,
  • the cooling rate influences the size of the ice crystals formed. These in turn influence the pore size distribution of the shaped body formed. If a few large crystals are formed, the shaped body has a small number of large pores. If many small crystals are formed, the shaped body has a large number of small pores. The higher the cooling rate of the solution or suspension, the smaller the crystals.
  • the freezing temperature that is required depends, among other things, on the extent to which the freezing point is lowered by the active substances or auxiliaries contained in the solution.
  • the temperature is expediently below the freezing point from water to the temperature of liquid nitrogen (- 1 96 ° C ),
  • the freezing temperature is preferably about -20 to -80 ° C, after the solution or suspension has been frozen, the moldings are removed from the mold and, if necessary, subjected to postprocessing, postprocessing can be carried out mechanically, for example by surface treatment (grinding, roughening Etc.).
  • a coating treatment is also possible, such as spraying with a salt solution, for example to form less soluble forms of the framework, especially when using sodium alginate and salt solutions of polyvalent metal ions.
  • a colored solution can also be applied superficially to the frozen moldings, which leads to colored moldings.
  • Freeze drying can be carried out in a manner known per se, as described, for example, in DE 4328329 02 or DE 4028622 C2.
  • the invention is illustrated in more detail by the following examples.
  • Example 4 (ball, diameter 1 2 mm)
  • Example 5 (ball, diameter 1 2 mm)
  • a mixture of 1.5 g of squalane and 0.01 g of ceramides is then added with stirring.
  • the homogeneous (degassed) mixture is poured into molds, frozen out with blowing air, removed from the mold and then freeze-dried in a manner known per se,

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  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/EP2003/010853 2002-10-16 2003-09-30 Verwendung von formkörpern zur äusseren anwendung WO2004035023A1 (de)

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US10/531,346 US9023333B2 (en) 2002-10-16 2003-09-30 Method of using shaped articles to apply a scaffold-forming agent to an external skin and/or hair surface of a human or an animal
EP03808702.9A EP1551373B1 (de) 2002-10-16 2003-09-30 Verwendung von formkörpern zur äusseren anwendung
AU2003276011A AU2003276011A1 (en) 2002-10-16 2003-09-30 Use of molded bodies for external application
ES03808702.9T ES2529568T3 (es) 2002-10-16 2003-09-30 Uso de cuerpos moldeados para aplicación externa
JP2005501273A JP2006504799A (ja) 2002-10-16 2003-09-30 形成物の身体表面への利用法

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DE10248314.0 2002-10-16
DE2002148314 DE10248314A1 (de) 2002-10-16 2002-10-16 Verwendung von Formkörpern zur äußeren Anwendung
DE10317982.8 2003-04-17
DE2003117982 DE10317982A1 (de) 2003-04-17 2003-04-17 Verwendung von Formkörpern zur äußeren Anwendung

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WO2004035023A8 WO2004035023A8 (de) 2004-06-03

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ES (1) ES2529568T3 (ja)
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WO2008020066A1 (de) * 2006-08-17 2008-02-21 Dr. Suwelack Skin & Health Care Ag Stabilisierte wirkstoffzusammensetzung
EP2243469A1 (de) 2009-04-22 2010-10-27 Dr. Suwelack Skin & Health Care AG Gefriergetrockneter Formkörper enthaltend Magnesiumascorbylphosphat
EP2243470A1 (de) 2009-04-22 2010-10-27 Dr. Suwelack Skin & Health Care AG Gefriergetrockneter beschichteter Formkörper
EP2243472A1 (de) 2009-04-22 2010-10-27 Dr. Suwelack Skin & Health Care AG Gefriergetrocknete Wirkstoffzusammensetzung

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GB2561818B (en) * 2017-03-30 2020-01-15 Phyto Sophos Ltd Plant extract compositions
WO2022066546A1 (en) 2020-09-22 2022-03-31 Swimc Llc Chitosan-containing coating compositions
CN115670941A (zh) * 2021-07-23 2023-02-03 嘉药学校财团法人嘉南药理大学 机能性悬浮造型晶球及其制造方法

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EP0352190A1 (fr) 1988-07-21 1990-01-24 Farmalyoc Nouvelle forme unitaire, solide et poreuse comprenant des microparticules et/ou nanoparticules ainsi que sa préparation
EP0362190A2 (de) 1988-09-28 1990-04-04 VOEST-ALPINE AUTOMOTIVE Gesellschaft m.b.H. Positionsgeber
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WO2008020066A1 (de) * 2006-08-17 2008-02-21 Dr. Suwelack Skin & Health Care Ag Stabilisierte wirkstoffzusammensetzung
EP2243469A1 (de) 2009-04-22 2010-10-27 Dr. Suwelack Skin & Health Care AG Gefriergetrockneter Formkörper enthaltend Magnesiumascorbylphosphat
EP2243470A1 (de) 2009-04-22 2010-10-27 Dr. Suwelack Skin & Health Care AG Gefriergetrockneter beschichteter Formkörper
EP2243472A1 (de) 2009-04-22 2010-10-27 Dr. Suwelack Skin & Health Care AG Gefriergetrocknete Wirkstoffzusammensetzung
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JP2006504799A (ja) 2006-02-09
JP2013173780A (ja) 2013-09-05
JP2018002746A (ja) 2018-01-11
US9023333B2 (en) 2015-05-05
JP5952774B2 (ja) 2016-07-13
JP2016041759A (ja) 2016-03-31
EP1551373A1 (de) 2005-07-13
WO2004035023A8 (de) 2004-06-03
EP1551373B1 (de) 2014-11-12
US20050281849A1 (en) 2005-12-22
ES2529568T3 (es) 2015-02-23
TW200413023A (en) 2004-08-01
AU2003276011A1 (en) 2004-05-04
TWI262796B (en) 2006-10-01
JP2010280704A (ja) 2010-12-16

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